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Lead halide perovskite possesses a semiconductor bandgap that is readily tunable by a variation in its halide composition. Here, a photo-activated halide exchange process between perovskite nanocrystals and molecular haloalkanes is reported, which enables the perovskite luminescence to be controllably shifted across the entire visible spectrum. Mechanistic investigations reveal a mutual exchange of halogens between the perovskite crystal surface and a chemisorbed haloalkane, yielding nanocrystals and haloalkanes with mixed halide contents. Exchange kinetics studies involving primary, secondary, and tertiary haloalkanes show that the rate of reaction is governed by the activation barrier in the breakage of the covalent carbon-halogen (CX) bond, which is a function of the CX bond energy and carbon radical stability. Employing this halide exchange approach, a micrometer-scale trichromatic patterning of perovskites is demonstrated using a light-source-integrated inkjet printer and tertiary haloalkanes as color-conversion inks. The haloalkanes volatilize after halide exchange and leave no residues, thereby offering significant processing advantage over conventional salt-based exchange techniques. Beyond the possible applications in new-generation micro-LED and electroluminescent quantum dot displays, this work exemplifies the rich surface and photochemistry of perovskite nanocrystals, and could lead to further opportunities in perovskite-based photocatalysis and photochemical sensing.

We demonstrate high resolution the IGZO-TFT of 4k/2k 65-inch panel in G6 glass. Two kinds of etch-stopper (ES) treatment power were used IGZO-TFT, i.e., low and high power treatment (LPT and HPT), respectively. We studied the electrical characteristics of IGZO-devices with LPT and HPT, including subthreshold slope (SS), threshold voltage (Vth), mobility, hysteresis, and Vt shift under positive and negative gate-bias temperature stress (PBTS and NBTS) with and without light illumination, respectively. The IGZO-TFT with HPT can be attributed to the dominant charge trapping located at GI/IGZO, IGZO/ES interface and in the IGZO film, whereas those with LPT are mainly due to charge trapping located at the GI/IGZO interface. Finally, the IGZO-devices with LPT can simultaneously achieve low SS, Vt, and little hysteresis, and high mobility, as compared with those with HPT, moreover, those with LPT under PBTS with and without light illumination exhibited lower Vt change than those with HPT.

Determine the presence of nasopharynx biofilms in patients with nasopharyngeal cancer (NPC) and osteoradionecrosis (ORN) and patients with NPC but no ORN.Cross-sectional study.Tertiary referral medical center.We enrolled 27 patients with NPC from our outpatient clinic during January 2010 to June 2012. These patients were diagnosed with NPC between 1980 and 2012, and all had received radiotherapy. Of these 27 patients, 15 presented with ORN, and 12 did not. The nasopharynx biopsied specimens were processed and analyzed within 2 hours of collection with the FilmTracer LIVE_DEAD Biofilm Viability Kit (Molecular Probes, Invitrogen, Carlsbad, California). A blinded investigator determined the formation of biofilms by fluorescence microscopy. Bacterial cultures were collected.Eleven of 15 (73%) ORN patients had biofilm formations in nasopharynx biopsy specimens. Five of these samples (45%) yielded positive cultures, and 4 of these cultures indicated the presence of methicillin-resistant Staphylococcus aureus (MRSA). Only 1 of 12 NPC patients without ORN had nasopharynx biofilm formation, and all culture results were negative.Biofilm formations were common in nasopharynx samples of NPC patients with ORN but rare in samples of NPC patients without ORN. The presence of biofilms, especially MRSA, may have a role in the disease progression of ORN or may contribute to the chronicity and resistance to antibiotic treatment.

Background and purpose: Tetracyclines were recently found to induce tumour cell death, but the early processes involved in this cytotoxic effect remain unclear. Experimental approach: Viability of human and mouse melanoma cells was determined by MTT assay and flow cytometry. Kinase/protein/caspase activation was measured by Western blotting and mitochondrial membrane potential (ΔΨm) was analyzed by fluorescence microscopy and flow cytometry. Key results: Human and mouse melanoma cells were treated with doxycycline or minocycline but only doxycycline was cytotoxic. This cell death (apoptosis) in A2058 cells involved activation of caspase-3, -7 and -9 and contributed to inhibition, by doxycycline, of matrix metalloproteinase (MMP) activity and migration of these cells. Doxycycline induced intra-cellular reactive oxygen species (ROS) production, apoptosis signal-regulated kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation at an early stage of treatment and induced mitochondrial cytochrome c release into cytosol and ΔΨm change during apoptosis. The JNK inhibitor/small interference RNA inhibited doxycycline-induced JNK activation, ΔΨm change and apoptosis, but did not affect ASK1 activation, suggesting a role of ASK1 for JNK activation in melanoma cell apoptosis. Two ROS scavengers reduced doxycycline-induced JNK and caspase activation, and apoptosis. Taken together, the results suggest the involvement of a ROS-ASK1-JNK pathway in doxycycline-induced melanoma cell apoptosis. Conclusions and implications: We have shown a promising cytotoxic effect of doxycycline on melanoma cells, have identified ROS and ASK1 as the possible initiators and have demonstrated that JNK activation is necessary for doxycycline-induced melanoma cell apoptosis.

Thrombin levels increase at sites of vascular injury and during acute coronary syndromes. It is also increased several fold by sepsis with a reciprocal decrease in the anti-thrombin III levels. In this study we investigate the effects of thrombin on the induction of cyclooxygenase-2 (COX-2) and prostaglandin (PG) production in macrophages. Thrombin-induced COX-2 protein and mRNA expression in RAW264.7 and primary cultured peritoneal macrophages. A serine proteinase, trypsin, also exerted a similar effect. The inducing effect by thrombin in macrophages was not affected by a lipopolysaccharide (LPS)-binding antibiotic, polymyxin B, excluding the possibility of LPS contamination. The increase of COX-2 expression by thrombin was functionally linked to release of PGE2 and PGI2 but not thromboxane A2 into macrophage culture medium. Thrombin-induced COX-2 expression and PGE2 production were significantly attenuated by PD98059 and SB202190 but not by SP600125, suggesting that ERK1/2 and p38 MAPK activation were involved in this process. This was supported by the observation that thrombin could directly activate ERK1/2 and p38 MAPK in macrophages. A further analysis indicated that the proteinase-activated receptor 1 (PAR1)-activating agonist induced effects similar to those induced by thrombin in macrophages and the PAR1 antagonist-SCH79797 could attenuate thrombin-induced COX-2 expression and PGE2 release. Taken together, we provided evidence demonstrating that thrombin can induce COX-2 mRNA and protein expression and PGE2 production in macrophages through PAR1 activation and ERK1/2 and p38 MAPK-dependent pathway. The results presented here may explain, at least in part, the possible contribution of thrombin and macrophages in these pathological conditions. J. Cell. Biochem. 108: 1143–1152, 2009. © 2009 Wiley-Liss, Inc.

The NaBH4 (or TBABH4)-promoted electrochemically reductive cleavage of aryl C–O bonds in diaryl ethers to produce phenols and arenes with high yields and excellent selectivities at room temperature was reported. Air- and water-tolerable, this process also works on the cleavage of aryl alkyl and benzyl ethers. The application to break the β-O-4, α-O-4, and 4-O-5 lignin model compounds is also illustrated, which highlights the advance toward the goal of lignin conversion.

It has been reported that ultraviolet B (UVB) irradiation causes the loss of E-cadherin of melanocytes, leading them to escape from neighboring keratinocytes during melanoma development. However, little has been paid on its effect on E-cadherin of keratinocytes. In the present study we therefore focus on whether UVB affects expression of E-cadherin-catenin complex in human HaCaT keratinocytes. We found that E-cadherin, beta-, and gamma-catenin but not alpha-catenin were proteolytically cleaved in UVB-irradiated HaCaT keratinocytes. The effect was only observed in keratinocyte undergoing apoptosis. Cleavage of beta- and gamma-catenin was fully abolished by caspase-3 and caspase-8 inhibitors, whereas cleavage of E-cadherin was inhibited by neither caspase nor metalloproteinase inhibitors. Functional analysis showed that the cleavage resulted in the disruption of the physical association between E-cadherin and catenins, indicating that E-cadherin signaling was compromised in UVB-irradiated HaCaT keratinocytes. Because E-cadherin in keratinocytes plays important roles in mediating cell-cell adhesion in epidermis of skin, the loss of E-cadherin and signaling components in keratinocytes may lead to the disruption of skin integrity after UVB exposure.

It is increasingly evident that the stromal cells are involved in key metastatic processes of melanoma and some malignant solid tumors. (-)-Epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, has been shown to have anti-tumor activity, inhibiting adhesion, migration, and proliferation of tumor cells. However, little attention has been paid on its effects on stromal cells. In the present study, we determined the effects of EGCG on stromal fibroblasts. We showed that fibroblast adhesion to collagen, fibronectin, and fibrinogen were inhibited by EGCG. One of the possible mechanisms is binding of EGCG to fibronectin and fibrinogen but not to collagen. We then focused how EGCG affected fibroblast adhesion to collagen. EGCG treatment attenuated the antibody binding to fibroblast's integrin alpha2beta1, indicating EGCG may affect the expression and affinity of integrin alpha2beta1. Moreover, intracellular H2O2 level was decreased by EGCG treatment, suggesting that the tonic maintenance of intracellular H2O2 may be required for cell adhesion to collagen. In parallel, collagen-induced FAK phosphorylation, actin cytoskeleton reorganization in fibroblasts, migration and matrix metalloproteinase(s) (MMPs) activity were also affected by EGCG. Tubular networks formed by melanoma cells grown on three-dimensional Matrigel were also disrupted when fibroblasts were treated with EGCG in a non-contact coculture system. Taken together, we provided here the first evidence that EGCG is an effective inhibitor on behaviors of the stromal fibroblasts, affecting their adhesion and migration. The inhibitory activity of EGCG may contribute to its anti-tumor activity. The findings and concepts disclosed here may provide important basis for a further experiment towards understanding tumor-stroma interaction.

Objectives:Chronic rhinosinusitis (CRS) is a chronic inflammatory disease involving the mucosa of the nasal cavity and sinuses. It can be classified into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). It is often described as a chronic inflammatory condition of the sinonasal mucosa and followed by a continuous tissue remodeling process. The CXC chemokine such as CXCL1 and CXCL8 are primarily chemotactic for endothelial cells and neutrophils, whch are potent promoters of angiogensis and inflammation.Methods:In this study, we examined the effects of kinin on CXC chemokine expression in human nasal fibroblasts from mucosa specimens of patients with CRSsNP.Results:We found kinin increased CXCL1 and CXCL8 release in a concentration- and time-dependent manner, as determined by enzyme-linked immunosorbent assay. In parallel, reverse transcriptase polymerase chain reaction analysis showed the kinin increased CXCL1 and CXCL8 mRNA level, suggesting this process involved transcriptional regulation...

Experiments were designed to differentiate the mechanisms and subtype of kinin receptors mediating the changes in intracellular Ca2+ concentration ([Ca2+]i) induced by bradykinin (BK) in canine cultured tracheal epithelial cells (TECs). BK and Lys-BK caused an initial transient peak of [Ca2+]i in a concentration-dependent manner, with half-maximal stimulation (pEC50) obtained at 7.70 and 7.23, respectively. Kinin B2 antagonists Hoe 140 (10 nM) and [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK (1 μM) had high affinity in antagonizing BK-induced Ca2+ response with pKB values of 8.90 and 6.99, respectively. Pretreatment of TECs with pertussis toxin (100 ng ml−1) or cholera toxin (10 μg ml−1) for 24 h did not affect the BK-induced IP accumulation and [Ca2+]i changes in TECs. Removal of Ca2+ by the addition of EGTA or application of Ca2+-channel blockers, verapamil, diltiazem, and Ni2+, inhibited the BK-induced IP accumulation and Ca2+ mobilization, indicating that Ca2+ influx was required for the BK-induced responses. Addition of thapsigargin (TG), which is known to deplete intracellular Ca2+ stores, transiently increased [Ca2+]i in Ca2+-free buffer and subsequently induced Ca2+ influx when Ca2+ was re-added to this buffer. Pretreatment of TECs with TG completely abolished BK-induced initial transient [Ca2+]i, but had slight effect on BK-induced Ca2+ influx. Pretreatment of TECs with SKF96365 and {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 inhibited the BK-induced Ca2+ influx and Ca2+ release, consistent with the inhibition of receptor-gated Ca2+ -channels and phospholipase C in TECs, respectively. These results demonstrate that BK directly stimulates kinin B2 receptors and subsequently phospholipase C-mediated IP accumulation and Ca2+ mobilization via a pertussis toxin-insensitive G protein in canine TECs. These results also suggest that BK-induced Ca2+ influx into the cells is not due to depletion of these Ca2+ stores, as prior depletion of these pools by TG has no effect on the BK-induced Ca2+ influx that is dependent on extracellular Ca2+ in TECs. Keywords: Bradykinin receptor, Ca2+, inositol phosphate, pertussis toxin, thapsigargin, tracheal epithelial cells Introduction Bradykinin (BK), one of the kinin family, is a classical mediator of inflammatory diseases of the airways and is implicated in allergic asthma (Christiansen et al., 1987; Farmer et al., 1991). In the airways, BK causes bronchoconstriction, pulmonary and bronchial vasodilatation, mucus secretion and microvascular leakage (Barnes, 1992). The physiological actions of BK are mediated through at least two distinct BK receptor subtypes, termed B1 and B2, which have been pharmacologically characterized using different kinin analogues with agonist and antagonist properties (Regoli & Barabe, 1980). Several lines of evidence demonstrate that activation of BK receptors leads to phospholipase C (PLC) activation resulting in phosphoinositide (PI) hydrolysis in the plasma membrane of different cell types (Balmforth et al., 1992; Marsh & Hill, 1992; Yang et al., 1994a; Smith et al., 1995). The resultant increase in inositol 1,4,5-trisphosphate (IP3) and diacylglycerol releases Ca2+ from internal stores and activates protein kinase C (PKC), respectively (Nishizuka, 1992; Horowitz et al., 1996). BK has been shown to stimulate chloride secretion in native canine tracheal epithelium (Leikauf et al., 1985), but the mechanisms involved in BK-induced secretory response are not completely understood. One of possible mechanisms implicated in regulation of secretory function of trachea may be attributable to an increase in PI hydrolysis mediated by kinin B2 receptors (Marsh & Hill, 1992; Yang et al., 1994a; 1995; Luo et al., 1996) and a rise in intracellular Ca2+ ([Ca2+]i) (Marsh & Hill, 1993; Yang et al., 1994b; Smith et al., 1995; Mathis et al., 1996). The elevation of [Ca2+]i has been thoroughly characterized in these cells, which is typified by an immediate and transient peak followed by a sustained phase. Three mechanisms have been proposed to be involved in BK-induced elevation of [Ca2+]i in these cells. Mobilization of Ca2+ from internal stores is suggested by the observation that elevation of [Ca2+]i induced by BK is partially preserved despite reduction of external Ca2+ concentrations, and is associated with the generation of IP3 (Marsh & Hill, 1993; Buchan & Martin, 1991). Ca2+ influx is also likely to contribute to the BK response, because the rise in [Ca2+]i induced by BK is attenuated when external Ca2+ is removed (Marsh & Hill, 1993; Yang et al., 1994b). In many cases, agonist-induced Ca2+ influx is blocked by drugs that inhibit dihydropyridine-sensitive, voltage-gated Ca2+ channels (Nelson et al., 1988; Yang et al., 1994b). However, some workers have found no effect of such drugs on BK-induced [Ca2+]i response (Murray & Kotlikoff, 1991), and have proposed that Ca2+ influx involves dihydropyridine-insensitive, voltage-gated channels or nonspecific cation channels. The biochemical mechanisms linking both the initial and sustained phases are not well defined in TECs. A capacitative entry model has been proposed by Putney (1993). In this model, Ca2+ influx can be activated by a process shunting second messengers such as IP metabolites, whereby the filling state of some Ca2+-stores alone is sufficient to induce Ca2+ entry. The evidence for supporting this hypothesis was obtained from studies using specific sarcoplasmic reticulum Ca2+-ATPase inhibitor, such as thapsigargin (TG), which has been proved to be useful in testing this hypothesis and emptying the intracellular Ca2+ pools without generating any known second messenger (Thastrup et al., 1990). The sustained increase in [Ca2+]i induced by TG is generally followed by an activation of Ca2+ influx, as shown in mast cells (Dar & Pecht, 1992), human platelets (Malcolm & Fitzpatrick, 1992), lacrimal acinar cells (Kwan et al., 1990) and neuronal cell lines (Takemura et al., 1991). These findings led us to suggest the existence, in canine TECs, of a similar signalling mechanism linking the filling state of intracellular Ca2+ pools and Ca2+ influx. We have previously reported that BK can induce an increase in PI hydrolysis which appears to be mediated via the activation of kinin B2 receptors in canine cultured TECs (Luo et al., 1996). To further define the cellular mechanisms that modulate intracellular [Ca2+]i, therefore, we have undertaken these studies to clarify, in part, the nature of changes in [Ca2+]i during continued exposure to BK in TECs. These results suggest that BK induces Ca2+ release from internal stores and Ca2+ influx from the extracellular milieu by distinct mechanisms. Furthermore, these results demonstrate that the activation of a calcium-release from intracellular stores and the activation of a calcium-entry through channels are independent effects which occur following stimulation of kinin B2 receptor by BK in canine cultured TECs.

1. Regulation of the increase in inositol phosphates (IPs) production and intracellular Ca2+ concentration ([Ca2+]i by protein kinase C (PKC) was investigated in canine cultured tracheal epithelial cells (TECs). Stimulation of TECs by bradykinin (BK) led to IPs formation and caused an initial transient [Ca2+]i peak in a concentration-dependent manner. 2. Pretreatment of TECs with phorbol 12-myristate 13-acetate (PMA, 1 microM) for 30 min attenuated the BK-induced IPs formation and Ca2+ mobilization. The maximal inhibition occurred after incubating the cells with PMA for 2 h. 3. The concentrations of PMA that gave half-maximal (pEC50) inhibition of BK-induced IPs accumulation and an increase in [Ca2+]i were 7.07 M and 7.11 M, respectively. Inactive phorbol ester, 4alpha-phorbol 12,13-didecanoate at 1 microM, did not inhibit these responses. Prior treatment of TECs with staurosporine (1 microM), a PKC inhibitor, inhibited the ability of PMA to attenuate BK-induced responses, suggesting that the inhibitory effect of PMA is mediated through the activation of PKC. 4. In parallel with the effect of PMA on the BK-induced IPs formation and Ca2+ mobilization, the translocation and down-regulation of PKC isozymes were determined. Analysis of cell extracts by Western blotting with antibodies against different PKC isozymes revealed that TECs expressed PKC-alpha, betaI, betaII, gamma, delta, epsilon, theta and zeta. With PMA treatment of the cells for various times, translocation of PKC-alpha, betaI, betaII, gamma, delta, epsilon and theta from cytosol to the membrane was seen after 5 min, 30 min, 2 h, and 4 h treatment. However, 6 h treatment caused a partial down-regulation of these PKC isozymes. PKC-zeta was not significantly translocated and down-regulated at any of the times tested. 5. Treatment of TECs with 1 microM PMA for either 30 min or 6 h did not significantly change the KD, and Bmax receptor for BK binding (control: KD=1.7+/-0.3 nM; Bmax=50.5+/-4.9 fmol/mg protein), indicating that BK receptors are not a site for the inhibitory effect of PMA on BK-induced responses. 6. In conclusion, these results suggest that activation of PKC may inhibit the phosphoinositide hydrolysis and consequently attenuate the [Ca2+]i increase or inhibit independently both responses to BK. The translocation of pKC-alpha, betaI, betaII, delta, epsilon, gamma, and theta induced by PMA caused an attenuation of BK-induced IPs accumulation and Ca2+ mobilization in TECs.

Due to the rapid progress in computers and communication networks, we may want to hold a secure electronic election on a public network. The election scheme that we proposed in this paper can fully conform the requirements of holding a large-scale election. The privacy of the voters can be preserved against the voting center. No one, including the voting center, knows which voting strategy each voter adopts. The voting center cannot present a false tally without being caught. Then, “Electronic Election” on a public network is possible by employing our proposed scheme. © 1997 John Wiley & Sons, Inc.

An efficient and metal-free method for the direct C–N coupling of indoles with azoles to produce 2-(azol-1-yl)indoles in aqueous solution has been developed. This reaction proceeded highly regioselectively to provide a variety of indole derivatives with good to excellent yields.

1. A direct [3H]-bradykinin ([3H]-BK) binding assay has been used to characterize the BK receptors in canine cultured tracheal epithelial cells (TECs). Based on receptor binding assay, TECs have specific, saturable, high-affinity binding sites for [3H]-BK. 2. The specific [3H]-BK binding was time- and temperature-dependent. Equilibrium of association of [3H]-BK with the BK receptors was attained within 30 min at room temperature and 1 h at 4 degrees C, respectively. 3. Analysis of binding isotherms yielded an apparent equilibrium dissociation constant (KD) of 1.5 +/- 0.2 nM and a maximum receptor density (Bmax) of 53.2 +/- 5.2 fmol mg-1 protein. The Hill coefficient for [3H]-BK binding was 1.00 +/- 0.02. The association (K1) and dissociation (K-1) rate constants were (7.6 +/- 1.1) x 10(6) M-1 min-1 and (9.2 +/- 1.5) x 10 M-3 min-1, respectively. KD, calculated from the ratio of K-1 and K1, was 1.2 +/- 0.3 nM, a value close to that calculated from Scatchard plots of binding isotherms. 4. Neither a B1 receptor selective agonist (des-Arg9-BK, 0.1 nM - 10 microM) nor antagonist ([Leu8, des-Arg9]-BK, 0.1 nM - 10 microM) significantly inhibited [3H]-BK binding to TECs, which excludes the presence of B1 receptors in canine TECs. 5. The specific binding of [3H]-BK to canine TECs was inhibited by the B2 receptor selective antagonists ([D-Arg0, Hyp3, Thi5, D-Tic7, Oic8]-BK (Hoe 140, 0.1 nM-10 microM) and [D-Arg0, Hyp3, Thi5.8, D-Phe7]-BK, 0.1 nM - 10 microM) and agonists (BK and kallidin, 0.1 nM-10 microM) with a best fit by a one-binding site model. The order of potency for the inhibition of [3H]-BK binding was kallidin = BK = Hoe 140 > [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK. 6. BK and kallidin significantly induced concentration-dependent accumulation of IPs with a half-maximal response (EC50) at 17.6 +/- 3.5 and 26.6 +/- 5.3 nM, respectively, while the B1-selective agonist, des-Arg9-BK did not stimulate IPs accumulation and the B1-selective antagonist [Leu8, des-Arg9]-BK did not inhibit BK-induced IPs accumulation. Two B2-selective antagonists, Hoe 140 and [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK, inhibited BK-stimulated IPs accumulation with apparent pKB values of 8.8 +/- 0.3 and 7.0 +/- 0.3, respectively. 7. It is concluded that the pharmacological characteristics of the BK receptors in canine cultured TECs are primarily of the B2 receptor subtype which might regulate the function of tracheal epithelium through the activation of this receptor subtype coupling to PI hydrolysis.